Morphological and physiological evidence suggests that cerebral blood vessels of several species receive both vasoconstrictor and vasodilator nerves and that norepinephrine (NE) and acetycholine (Ach) are the respective transmitter substances. Our recent in vitro studies suggest that NE is merely one of the multiple transmitters for the vasoconstrictor nerves and Ach is not the transmitter for the vasodilator nerve in rabbit and cat cerebral arteries. Conclusions from in vivo studies of vasomotor role of the innervation have also been conflicting. The disparity in findings might be due to species differences and the various experimental conditions used in vivo. The possibility of hypertension-related variation, however, has not been examined. The purpose of this study is to delineate the nature of cerebral vessel innervation, especially in relation to hypertension by in vitro techniques. Ancillary techniques of biochemical analysis and morphology (electron microscopy and fluorescence microscopy) will be utilized to provide a relatively comprehensive multifaceted approach to this problem. Specifically, studies will be designed to determine (1) the nature of transmitter substance for vasodilation, (2) the characteristics of nerve endings and their relationship to the vascular smooth muscle cells, and (3) the hypertension-related variation in, and funcional significance of, vasoconstrictor and dilator innervation of cerebral blood vessels. This research is a step toward our long-term goal to define the functional significance of cerebral blood vessel innervation.